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PubMed1999

Left atrial appendage: structure, function, and role in thromboembolism.

The left atrial appendage (LAA) is derived from the left wall of the primary atrium, which forms during the fourth week of embryonic development. It has developmental, ultrastructural, and physiological characteristics distinct from the left atrium proper. The LAA lies within the confines of the pericardium in close relation to the free wall of the left ventricle and thus its emptying and filling may be significantly affected by left ventricular function. The physiological properties and anatomical relations of the LAA render it ideally suited to function as a decompression chamber during left ventricular systole and during other periods when left atrial pressure is high. These properties include the position of the LAA high in the body of the left atrium; the increased distensibility of the LAA compared with the left atrium proper; the high concentration of atrial natriuretic factor (ANF) granules contained within the LAA; and the neuronal configuration of the LAA. Thrombus has a predilection to form in the LAA in patients with atrial fibrillation, mitral valve disease, and other conditions. The pathogenesis has not been fully elucidated; however, relative stasis which occurs in the appendage owing to its shape and the trabeculations within it is thought to play a major role. Obliteration or amputation of the LAA may help to reduce the risk of thromboembolism, but this may result in undesirable physiological sequelae such as reduced atrial compliance and a reduced capacity for ANF secretion in response to pressure and volume overload.

Atrial Appendage↗
PubMed1996

Synthetic studies on polysaccharide HS-142-1, a novel nonpeptide antagonist for the atrial natriuretic peptide receptor: syntheses of the gentiobiosyl fragments.

Possible disaccharide fragments of the major component of HS-142-1, a novel polysaccharide antagonist for functional atrial natriuretic peptide (ANP) receptors, O-(4-O-caproyl-beta-D-glucopyranosyl)-(1 --> 6)-4-O-caproyl-D-glucopyranose (1) and O-(3-O-caproyl-beta-D-glucopyranosyl)-(1 --> 6)-3-O-caproyl-D-glucopyranose (2), were respectively synthesized in a stereo- and regio-controlled manner. Deprotection of 2,2'-di-O-caproyl derivative 35 gave a complex mixture due to undesired acyl migration. In contrast, 2,4'-di-O-caproyl analog 39 was successfully deprotected to give O-(4-O-caproyl-beta-D-glucopyranosyl)-(1 --> 6)-2-O-caproyl-D-glucopyranose (40).

Carbohydrate Conformation↗
PubMed1997

[Atrial sensing and atrioventricular synchrony in single lead VDD pacemakers. Can the appearance of atrial undersensing be predicted?].

Single-lead VDD-pacing is an alternative to DDD-systems in patients with AV-block and normal sinus node function. Atrial sensing plays a central role in these pacemakers. AV-synchrony, incidence of atrial arrhythmias and the occurrence of sinus node disease were investigated in 108 patients with VDD-pacemakers followed over a mean period of 24.8 months after implantation. Determinants influencing the occurrence of atrial undersensing were especially focused on. Mean atrial potential and sensing threshold were reduced within the first 2 weeks after implantation (p < 0.01). Intermittent atrial undersensing occurred in 25.9% of patients and was observed in 82.1% of these patients within the first 2 weeks after implantation. Positioning the atrial dipole in the low right atrium showed a significantly higher incidence of atrial undersensing (42% in comparison to 24% in the other positions). In a multivariate analysis including intra- and postoperative measurements as well as characteristics of the pacemakers and leads, it was the only parameter significantly (p < 0.02) correlated to the occurrence of atrial undersensing. Atrial fibrillation was observed in 4.6% of patients, a sinus node disease became evident in 2.7% of patients; 92.6% of patients remained in the AV-synchronous mode. Intermittent atrial undersensing is common in single-lead VDD-pacemakers and difficult to provide during implantation. The atrial dipole should not be positioned in the low right atrium and highest atrial sensitivity should generally be programmed. Nevertheless, VDD-pacing achieves an AV-synchrony comparable to DDD-pacemakers.

Aged↗
PubMed2004

Successful performance of Cox-Maze procedure on beating heart using bipolar radiofrequency ablation: a feasibility study in animals.

BACKGROUND: The Cox-Maze procedure is the gold standard for the surgical treatment of atrial fibrillation with proven long-term efficacy. However, its application has been limited by its complexity and significant morbidity. The purpose of this study was to test the feasibility and safety of performing the Cox-Maze procedure using bipolar radiofrequency ablation on the beating heart without cardiopulmonary bypass. METHODS: After median sternotomy, 6 Hanford mini-pigs underwent a modified Cox-Maze procedure using bipolar radiofrequency energy. The animals survived for 30 days. Atrial function, coronary artery, pulmonary vein anatomy, and valve function were assessed by magnetic resonance imaging. At reoperation, pacing documented electrical isolation of the pulmonary veins. Induction of atrial fibrillation was attempted by burst pacing with cholinergic stimulation. Histologic assessment was performed after sacrifice. RESULTS: There were no perioperative mortalities or neurologic events. At 30 days, atrial fibrillation was unable to be induced, and pulmonary vein isolation was confirmed by pacing. Magnetic resonance imaging assessment revealed no coronary artery or pulmonary vein stenoses. Although atrial ejection fraction decreased slightly from 0.344 +/- 0.0114 to 0.300 +/- 0.055 (p = 0.18), atrial contractility was preserved in every animal. Histologic assessment showed all lesions to be transmural, and there were no significant stenoses of the coronary vessels or injuries to the valves. CONCLUSIONS: Virtually all of the lesions of the Cox-Maze procedure can be performed without cardiopulmonary bypass using bipolar radiofrequency energy. There were no late stenoses of the pulmonary veins. Clinical trials of this new technology on the beating heart are warranted.

Animals↗
PubMed2002

Anticoagulation for cardioversion of atrial fibrillation.

The cardioversion of chronic atrial fibrillation to sinus rhythm carries a thromboembolic risk of 1.5-6%. These events occasionally occur at the time of cardioversion, but more often happen hours or days later. These strokes and other embolic events may occur even where atrial thrombus has been excluded before cardioversion and it has become apparent that, although atrial electrical activity may be restored by cardioversion, normal mechanical atrial function may take longer to recover. Numerous studies have addressed the role of anticoagulation following cardioversion in patients with atrial fibrillation, however, the mechanism of embolic complications as well as the justification of a standard anticoagulation therapy are not fully established. In this review we will try to present an overview of the mechanisms of thrombosis following cardioversion and give an insight into current anticoagulation strategies.

Acute Disease↗
PubMed1991

Therapeutic approaches affecting diastolic ventricular function.

The therapeutic approaches affecting diastolic ventricular function are conditional on underlying physiology, especially as it relates to calcium cycling, early relaxation and rapid filling abnormalities, atrial function, hemodynamics, the presence of hypertrophy, and neurohormonal milieu. A wide variety of treatment considerations are discussed, with particular attention to the management of cardiomyopathy characterized by pure or predominant diastolic failure (Table 1).

Cardiovascular Agents↗
PubMed1999

Gene expression of proteins influencing the calcium homeostasis in patients with persistent and paroxysmal atrial fibrillation.

OBJECTIVE: Persistent atrial fibrillation (AF) results in an impairment of atrial function. In order to elucidate the mechanism behind this phenomenon, we investigated the gene expression of proteins influencing calcium handling. METHODS: Right atrial appendages were obtained from eight patients with paroxysmal AF, ten with persistent AF (> 8 months) and 18 matched controls in sinus rhythm. All controls underwent coronary artery bypass grafting, whereas most AF patients underwent Cox's MAZE surgery (n = 12). All patients had a normal left ventricular function. Total RNA was isolated and reversely transcribed into cDNA. In a semi-quantitative polymerase chain reaction the cDNA of interest and of glyceraldehyde-3-phosphate dehydrogenase were coamplified and separated by ethidium bromide-stained gel electrophoresis. Slot blot analysis was performed to study protein expression. RESULTS: L-type calcium channel alpha 1 and sarcoplasmic reticulum Ca(2+)-ATPase mRNA (-57%, p = 0.01 and -28%, p = 0.04, respectively) and protein contents (-43%, p = 0.02 and -28%, p = 0.04, respectively) were reduced in patients with persistent AF compared to the controls. mRNA contents of phospholamban, ryanodine receptor type 2 and sodium/calcium exchanger were comparable. No changes were observed in patients with paroxysmal AF. CONCLUSIONS: Alterations in gene expression of proteins involved in the calcium homeostasis occur only in patients with long-term persistent AF. In the absence of underlying heart disease, the changes are rather secondary than primary to AF.

Aged↗
PubMed2005

Endocardial radiofrequency ablation during mitral valve surgery: effect on cardiac rhythm, atrial size, and function.

BACKGROUND: Restoration of sinus rhythm is thought to lead to a reduction in left atrial size and to recovery of atrial contraction. We aimed to investigate changes in atrial size and function in patients undergoing radiofrequency ablation for atrial fibrillation during mitral valve surgery. METHODS: In a prospective study, 70 patients (64 +/- 10 years) with mitral valve disease and atrial fibrillation underwent mitral surgery and left atrial endocardial radiofrequency ablation. Evaluation was achieved before surgery, at 7 days, 5 months, and 22 months after surgery. Maximal right and left atrial areas, left atrial diameter, and volume were measured. Atrial filling fraction (ventricular filling related to atrial contraction to total ventricular filling ratio) was used as an index of atrial contraction. RESULTS: At the end of follow-up (22 +/- 10 months) most patients (91%) were in sinus rhythm. Actuarial freedom from atrial fibrillation recurrence was 62.5% after 2 years. Atrial size decreased, with a significant improvement in right (36 +/- 15 vs 10 +/- 20% preoperatively, p < 0.0001) and left (25 +/- 12 vs 7 +/- 14%, p < 0.0001) atrial filling fraction. Despite similar preoperative atrial size, at the end of follow-up atrial fibrillation recurrence was associated with a higher left atrial volume than in patients free of recurrence (41 +/- 14 vs 32 +/- 9 mL/m2, p = 0.004). Independent predictors of atrial fibrillation recurrence were previous mitral procedure (p = 0.029), left ventricular ejection fraction (p = 0.033), and mitral rheumatic lesion (p = 0.034). CONCLUSIONS: Left atrial radiofrequency ablation for atrial fibrillation during mitral surgery is an effective procedure restoring sinus rhythm. Right and left atrial size was significantly reduced, with a recovery in atrial contraction.

Adult↗
PubMed1999

Transesophageal echocardiographic evidence of more pronounced left atrial stunning after chemical (propafenone) rather than electrical attempts at cardioversion from atrial fibrillation.

We studied left atrial function in 55 patients undergoing electrical (n = 23) or chemical (intravenous administration of propafenone, n = 32) attempts at cardioversion from atrial fibrillation. Chemical attempts at cardioversion revealed a significant increase in spontaneous echo contrast and a significant decrease in left atrial appendage Doppler flow, even in patients who did not have successful conversion to sinus rhythm.

Adult↗
PubMed2000

Hemodynamically optimized temporary cardiac pacing after surgery for congenital heart defects.

Disturbance of normal AV synchrony and dyssynchronous ventricular contraction may be deleterious in patients with otherwise compromised hemodynamics. This study evaluated the effect of hemodynamically optimized temporary dual chamber pacing in patients after surgery for congenital heart disease. Pacing was performed in 23 children aged 5 days to 7.7 years (median 7.3 months) with various postoperative dysrhythmias, low cardiac output, and/or high inotropic support and optimized to achieve the highest systolic and mean arterial pressures. The following four pacing modes were used: (1) AV synchronous or AV sequential pacing with individually optimized AV delay in 11 patients with first- to third-degree AV block; (2) AV sequential pacing using transesophageal atrial pacing in combination with a temporary DDD pacemaker for atrial tracking and ventricular pacing in three patients with third-degree AV block and junctional ectopic tachycardia, respectively, who had poor signal and exit block on atrial epicardial pacing wires; (3) R wave synchronized atrial pacing in eight patients with junctional ectopic tachycardia and impaired antegrade AV conduction precluding the use of atrial overdrive pacing; (4) Atrio-biventricular sequential pacing in two patients. Pressures measured during optimized pacing were compared to baseline values at underlying rhythm (13 patients with first-degree AV block or junctional ectopic tachycardia) or during pacing modes commonly used in the given clinical situation: AAI pacing (1 patient with slow junctional rhythm and first-degree AV block during atrial pacing), VVI pacing (2 patients with third-degree AV block and exit block and poor sensing on epicardial atrial pacing wires) and dual-chamber pacing with AV delays set to 100 ms (atrial tracking) or 150 ms (AV sequential pacing) in 7 patients with second- to third-degree AV block and functional atrial pacing wires. Optimized pacing led to a significant increase in arterial systolic (mean) pressure from 71.5 +/- 12.5 (52.3 +/- 9.0) to 80.5 +/- 12.2 (59.7 +/- 9.1) mmHg (P < 0.001 for both) and a decrease in central venous (left atrial) pressure from 12.3 +/- 3.4 (10.5 +/- 3.2) to 11.0 +/- 3.0 (9.2 +/- 2.7) mmHg (P < 0.001 and < 0.005, respectively). In conclusion, several techniques of individually optimized temporary dual chamber pacing leading to optimal AV synchrony and/or synchronous ventricular contraction were successfully used to improve hemodynamics in patients with heart failure and selected dysrhythmias after congenital heart surgery.

Arrhythmias, Cardiac↗
PubMed2006

Paroxysmal atrial flutter caused by cardiac lymphoma.

Atrial flutter is a relatively frequent macro-reentrant tachycardia that can be caused by a variety of structural and functional atrial changes. Cardiac lymphoma is rare and usually carries a poor prognosis. It preferentially involves the right atrium. This report describes a patient with cardiac follicular B-cell lymphoma who developed paroxysmal atrial flutter. The large tumor mass created a macroscopic substrate for an area of slow conduction which is essential for atrial flutter. It also caused sinus arrest and intermittent obstruction of the tricuspid valve inlet.

Aged↗
PubMed1988

The effects of 4-pentenoic and pentanoic acids on the isolated rat atria.

The peak developed tension and the pacemaker frequency of the isolated atria from fed and fasted rats, declined progressively during the incubation in a glucose-free medium containing 2-deoxyglucose. The atria from fed rats exhibited a faster decline than those from fasted rats, which was associated to a slower triacylglycerol lipolysis. 4-Pentenoic acid inhibited the lipolysis of both groups of atria but did not alter the atrial contractile performance. However, it enhanced the decline of the pacemaker frequency in the atria from fasted rats whereas, in contrast, it alleviated the decline in the fed atria. n-Pentanoic acid ameliorated the impairment of the contractile and pacemaker activities in both groups of atria, without affecting the lipolysis. It was concluded that, since the inhibition of the intramyocardial lipolysis did not correlate with changes of the atrial functions, 4-pentenoic acid was not appropriate to assess about the contribution of endogenous triacylglycerol to the maintenance of the atrial contractile and pacemaker activities.

Animals↗
PubMed1993

[Paroxysmal atrial fibrillation: the significance of the dynamic behavior of the atrial cycle].

The aim of this study was to evaluate the dynamic atrial endocardial activation pattern during atrial fibrillation and to investigate the electrophysiologic changes related to the self-termination of the arrhythmia. Twenty patients with daily recurrences of lone paroxysmal atrial fibrillation episodes underwent electrophysiological study with contemporary recording of the atrial signal in high right atrium, low right atrium and coronary sinus. Sixty episodes lasting longer than 1 min were recorded, 22 spontaneous and 38 induced with a single extrastimulus. A significant correlation has been demonstrated for the mean of 100 consecutive intervals evaluated at the arrhythmia onset and the atrial functional refractory period (R = 0.73, p < 0.001). Mean FF length increased significantly in the minute preceding self-termination of atrial fibrillation in all the 3 recording sites. On the contrary, a significant decrease of mean FF length was documented in long lasting episodes. Self-termination of atrial fibrillation episodes implies a peculiar pattern of intra-atrial interval. Therefore the analysis of FF intervals seems to have pathophysiological implication and may be applied also to evaluate pharmacological interventions.

Adolescent↗
PubMed1984

Maturational changes in ventriculoatrial conduction in the intact canine heart.

This study reports on the changes in ventriculoatrial (VA) conduction that occur with maturation. Programmed atrial and ventricular premature extra-stimulation (coupled to a fixed paced cycle length) and rapid atrial pacing were performed in three groups of dogs: Group I = 8 neonates aged 5 to 14 days, Group II = 9 young dogs aged 6 to 9 weeks and Group III = 10 adult dogs. High right atrial, His bundle and right ventricular electrograms were recorded. There were no differences in the AH intervals at rest. In all but five animals, atrioventricular conduction was limited by the atrial functional refractory period (Group I, 109 +/- 12 ms; Group II, 152 +/- 22 ms; Group III, 167 +/- 19 ms). As expected, with rapid atrial pacing, Wenckebach conduction developed at a shorter cycle length in the younger animals (Group I, 145 +/- 20 ms; Group II, 153 +/- 15 ms; Group III, 200 +/- 25 ms, p less than 0.01). Ventriculoatrial conduction was documented in 87% of Group I puppies and 100% of Group II, but only 40% of Group III dogs. The effective and functional refractory periods of the VA conduction system were significantly shorter in the more immature groups of dogs (effective/functional: Group I, 124 +/- 27/168 +/- 22 ms; Group II, 139 +/- 23/202 +/- 13 ms; Group III, 270 +/- 28/326 +/- 25 ms; p less than 0.01). Relative to the adult dog, the immature heart showed a greater incidence of VA conduction and shorter VA refractory periods. This enhanced VA conduction may be of physiologic importance in the initiation and perpetuation of certain supraventricular arrhythmias.

Age Factors↗
PubMed1998

Exercise capacity in patients with beta-thalassemia major: relation to left ventricular and atrial size and function.

OBJECTIVES: The objective of this study was to examine the association between exercise capacity and echocardiographic indexes of atrial and ventricular function and size in patients with beta-thalassemia major. BACKGROUND: In patients with beta-thalassemia major, the assessment of cardiac function with echocardiography alone does not always correspond to their functional status. Peak oxygen uptake and anaerobic threshold, on the other hand, constitute 2 objective and reproducible determinants of exercise capacity in patients with heart failure. METHODS AND RESULTS: Forty consecutive patients (22 women and 18 men, 18 to 30 years old) who were in stable condition while receiving regular transfusions and 30 age- and sex-matched control subjects were studied. At 2 to 3 days after the last transfusion, each subject underwent complete echocardiographic study followed by cardiopulmonary exercise testing. Left atrial volumes (maximal [Vmax], at onset of atrial systolic [Vp], and minimal [Vmin]) and left ventricular volumes were measured with the biplane area-length method, and left atrial active emptying fraction (ACTEF) and left ventricular ejection (LVEF) fraction were calculated. Peak oxygen uptake (Vo 2 max) and anaerobic threshold (AT) were also estimated. After transfusion, patients with beta-thalassemia major had reduced Vo 2 max and AT and greater left atrial volume in comparison with control subjects. Also, ACTEF and LVEF were significantly lower in the patient group. Moreover, Vo2 max and AT were inversely related to Vmax (r = -0.74 and r = -0.80, respectively) and directly related to ACTEF (r = 0.85 and r = 0.82, respectively) in beta-thalassemia major, whereas they were poorly related to LVEF (r = 0.50 and r = 0. 53, respectively). In the control group, Vo 2 max and AT parameters were related to Vmax and ACTEF in a similar way to that in the beta-thalassemia group. CONCLUSIONS: In patients with beta-thalassemia major, exercise capacity does not correlate with left ventricular dimensions and function. On the contrary, left atrial size and systolic dysfunction are probably predictors of decreased exercise capacity.

Adolescent↗
PubMed1983

Alterations in cardiac performance in experimentally-induced diabetes.

Responses in cardiac tissue isolated from streptozotocin (STZ)-treated and age-matched control rats to isoproterenol (ISO) and calcium were studied. 4 weeks after STZ, atrial function was found to be depressed, whereas right ventricular function was enhanced. Neither tissue exhibited an alteration in sensitivity to ISO. In contrast, while sensitivity to calcium was found to be unaltered in atrial tissue, supersensitivity to calcium was observed in ventricles after STZ treatment. beta-Adrenoceptor number determination revealed a 36% decrease in Bmax with no change in affinity after STZ treatment. These results suggest that 4 weeks after STZ treatment pacemaker function is depressed, while enhancement in ventricular function is associated with an alteration in calcium utilization.

Animals↗
PubMed2004

Dementia in subjects with atrial fibrillation: hemostatic function and the role of anticoagulation.

BACKGROUND: Atrial fibrillation (AF) is associated with cognitive impairment and dementia, perhaps through encouraging a prothrombotic state and cardioembolism. OBJECTIVES: We wished to test the hypotheses that hemostatic function is altered in subjects with AF who develop dementia, and that long-term warfarin anticoagulation is protective against this complication. PATIENTS AND METHODS: Recruitment was from an observational cohort study of AF. Baseline assessment included measurement of plasma fibrinogen, fibrin D-dimer, prothrombin fragment 1+2 (F1+2), thrombin-antithrombin complexes (TAT), von Willebrand factor and tissue plasminogen activator. We assessed cognitive function after 3 years' follow-up using the 13-item modified Telephone Interview for Cognitive Status (TICSm) and the short form of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). RESULTS: Of the 218 subjects assessed, 145 (66%) were prescribed warfarin. Forty-nine (22%) met TICSm/IQCODE criteria for dementia. D-dimer, F1+2 and TAT levels were higher in AF subjects with dementia compared with those without (medians 81 vs. 60 ng mL(-1), P = 0.008; 0.76 vs. 0.49 nmol L(-1), P = 0.006; and 1.78 vs. 1.44 microg L(-1), P = 0.003, respectively). These associations became of borderline statistical significance following adjustment for age. Logistic regression showed a trend towards warfarin use being independently associated with reduced prevalence of dementia (odds ratio 0.52, P = 0.08). CONCLUSIONS: We found evidence of increased thrombin generation and fibrin turnover in subjects with AF and dementia compared with those without dementia. Long-term warfarin use may be protective against the development of dementia in subjects with AF.

Aged↗
PubMed1977

Cardiac function in total anomalous pulmonary venous return before and after surgery.

Cardiac performance was evaluated in 12 infants with isolated total anomalous pulmonary venous return. Four had significant pulmonary venous obstruction and severe pulmonary hypertension (group A). Eight had no obvious venous obstruction, and the pulmonary pressures were lower (group B). In all subjects, right ventricular end-diastolic volume was increased (197% of predicted normal) and its ejection fraction was normal. Left ventricular volume was, generally speaking, still in the normal range (87% of predicted normal); however, its ejection fraction was reduced (0.57 vs normal of 0.73) and left ventricular output was low (3.08 L/min/m2 vs normal of 3.98). Left atrial volume was consistently small (53% of predicted normal) with an appendage of normal size. The infants in group A had smaller chamber volumes/m2 BSA than those in group B. Left atrial function was abnormal, characterized by reduced reservoir function and a greater role as "conduit" from right atrium to left ventricle. Left atrial size was not found to be critical in the surgical repair of TAPVR. Cardiac function is restored to normal following surgery.

Angiocardiography↗